The defective ability of aged mice to control Trypanosoma musculi infection prior to the onset of immune elimination is likely to be a reflection of the effects of senescence on the innate defense system (IDS). The latter is composed of three types of cells, dendritic cells (DC), macrophages (MP) and natural killer cells (NKC), the cytokines they produce, and elements of complement. We will test the concept that aging impairs the IDS. The research plan is divided into four "Tasks" including: optimizing the in vitro simulation of the IDS; comparing the functions of NKC (and activated LAK cells), DC and MP from young and aged mice within the IDS context; pinpointing the defective elements of the aged IDS; identifying the initial event that triggers IDS response and determining whether or not it is affected by aging. To our knowledge, this will be the first attempt to study aging of the IDS as a system. If we find that the murine IDS suffers from aging, it will become important to learn whether or not the same occurs in elderly humans and seek ways to selectively enhance IDS function. Another benefit of this research should be an excellent system for analyzing mechanisms of the innate control of infection that occurs preceding the more-slowly developing acquired immune response.